Synaptobrevins are synaptic vesicle-associated membrane proteins (VAMPs) which were first discovered in rat brain. These proteins were initially thought to be limited to neuronal cells and to function in the movement of vesicles from the plasmalemma of one cell, across the synapse, to the plasmalemma of another cell. Synaptobrevins are now known to occur and function in constitutive vesicle trafficking pathways involving receptor-mediated endocytotic and exocytotic pathways of many non-neuronal cell types. This regulated vesicle trafficking pathway may be blocked by the highly specific action of clostridial neurotoxins which cleave the synaptobrevin molecule.
In vitro studies of various cellular membranes (Galli et al (1994) J Cell Biol 125:1015-24; Link et al (1993) J Biol Chem 268:18423-6) have shown that VAMPS including the synaptobrevins, cellubrevins, and synaptogyrins are widely distributed. These important membrane trafficking proteins appear to participate in axon extension via exocytosis during development, in the release of neurotransmitters and modulatory peptides, and in endocytosis. Endocytotic vesicular transport includes such intracellular events as the fusions and fissions of the nuclear membrane, endoplasmic reticulum, Golgi apparatus, and various inclusion bodies such as peroxisomes or lysosomes. Endocytotic processes appear to be universal in eukaryotic cells as diverse as yeast, Caenorhabditis elegans, Drosophila, and mammals.
A synaptobrevin-binding protein required for neurotransmitter release was recently isolated from the neurons of Aplysia californica. Expression of the encoding cDNA in bacteria produced a 206 amino acid polypeptide with a molecular mass of 33 kD (VAP-33). The primary structure of VAP-33 showed similarity to an extracellular sperm protein, and functional analysis suggested its association in the exocytosis of synaptic vesicles (Skelhel, P. A. et al. (1995) Science 269: 1580-82).
Elucidation of the interactions between synaptobrevins, docking proteins, and core fusion proteins (Bark I C and Wilson M C (1994) Proc Natl Acad Sci 91:4621-4624) provide means for the regulation of membrane fusion and fission in normal as well as acute and chronic disease situations. The discovery of human vesicle binding protein and the polynucleotides encoding it satisfies a need in the art by providing a means for diagnosis, prevention, and treatment of inflammation and disorders of cell proliferation.